The use of a high-gradient magnetic field to attract and separate magnetically labelled particles from a fluid in which they are suspended is well known. Moreover, magnetic separation devices are used in a variety of industries including pharmaceutical, medical, agricultural, scientific and engineering fields. For example in biotechnology, a high-gradient magnetic field may be used to separate magnetically labelled bone marrow cells from a blood sample.
A high-gradient magnetic field is conventionally created by configuring magnets to provide a magnetic field with regions of high magnetic field density and regions of low magnetic field density. The gradient of the magnetic field is the variation in field strength between the high density regions and low density regions.
European Patent Application No 03819654 describes how a magnetic material may be used for collecting micrometer sized magnetic particles (preferably in the range of 0.1 to 2 μm). The magnetic material includes a plurality of magnets. Each magnet has a north pole and a south pole. The magnets are stacked one above the other in such a manner that the adjacent magnets are in contact with one another and the north poles (N) and south poles (S) of adjacent magnets are arranged alternately (i.e. the north pole (N) of a each magnet is arranged adjacent to the south pole (S) of an adjacent magnet). In order to collect magnetically labelled particles, the magnetic material is placed proximate a sample vessel such that a sample comprising magnetically labelled particles is subject to a “fringe” magnetic field (i.e. a magnetic field extending around the periphery of the magnetic material between opposing poles). It has been found that the strength and gradient of the fringe magnetic field is compromised as a result of placing magnets in contact with one another. The strength of the fringe magnetic field is limited because the return flux travels directly through the contacting adjacent magnets to the opposite poles rather than travelling outwardly around the periphery of the magnets towards the opposite poles of adjacent magnets. Since the strength of the fringe field is limited, the variation in field strength between the high magnetic field density regions and low magnetic field density regions of the fringe field is restricted. As a direct consequence, the gradient of the fringe magnetic field is minimised. The performance of the magnetic material is compromised as a result of placing the magnets in contact with one another. For example, the magnetic material may not be able to isolate the smallest micrometer sized particles and will be unsuitable for isolating nanometer sized particles. The efficiency and accuracy of the separation process will also be restricted.
U.S. patent application Ser. No. 10/484,110 describes a system for separating magnetically attractable micrommeter sized particles (preferably in the range of 1.5 to 4 μm) which are suspended in a liquid. The system includes a magnet arrangement that comprises at least two magnets in ring form. In a first embodiment of the system the magnet axis (Y-Y′) is orientated perpendicular to the ring plane and the magnets are arranged one above another in the same direction so that the north-south axes (Y-Y′) face in the same direction. The inner portions of the ring magnets form a space for receiving a sample vessel. FIG. 1a depicts a magnetic arrangement (15) comprising three ring magnets (10,10′,10″) arranged in the same direction. Non-magnetic spacers (11,11′) are arranged between adjacent ring magnets. A sample vessel (20) is arranged within a receiving space (12) of the magnet arrangement. FIG. 1b depicts the magnetic field generated by the magnet arrangement shown in FIG. 1a. The magnetic field acting within the receiving space is a fringe magnetic field (25). It is clear from the lines of magnetic flux shown in FIG. 1b that the magnetic field acting within the receiving space is a weak fringe magnetic field with a low gradient. The magnetic field is weak and has a low gradient due to the configuration of the ring magnets. The ring magnets are configured such that the magnetic flux travels directly through the magnets towards opposing poles rather than outwardly around the periphery of the magnets within the receiving space. Also, significant magnetic flux extends through the top and bottom pole faces rather than within the receiving space. Non-magnetic spacers provided between the ring magnets are intended to help create regions of low magnetic field density within the ring space. However, the spacers have very little effect on the gradient of the fringe field because the fringe field is already so weak. Since the fringe magnetic field is poor the efficiency and accuracy of the separation process is compromised. The size of particles that can be separated by the magnet arrangement is also restricted. More particularly, the magnet arrangement will be unsuitable for isolating smaller (nanommeter sized) magnetically labelled particles.
In a second embodiment of the system described in U.S. patent application Ser. No. 10/484,110 the ring magnets are arranged in opposite directions so that the north-south axes (Y-Y′) of adjacent magnets are in opposite directions. FIG. 2a depicts a magnet arrangement (15′) comprising three ring magnets (10,10′,10″) arranged in opposite directions. Non-magnetic spacing means (11,11′) are arranged between adjacent magnets. FIG. 2b depicts the magnetic field generated by the magnet arrangement of FIG. 2a. FIG. 2c depicts a graph showing how the magnetic field strength in the centre of the receiving space (12) varies along the central longitudinal axis (X-X′) of the magnet arrangement. It is clear from the flux lines of FIG. 2b that a stronger and higher gradient fringe magnetic field is generated within the receiving space when the ring magnets are arranged in opposite directions. This is because more magnetic flux is directed outwardly within the receiving space due to the repelling poles. The non-magnetic spacing means help to create regions of low magnetic field density within the receiving space. Due to the increased magnetic flux and use of non-magnetic spacing means the difference in the field strength between the regions of high magnetic field density and low magnetic field density is greater than in the first embodiment. Therefore, the gradient of the fringe magnetic field is higher than in the first embodiment. Nevertheless, the field strength and gradient of the fringe magnetic field acting within the receiving space is still restricted because significant magnetic flux continues to extend through the top and bottom pole faces of the ring magnet arrangement rather than within the receiving space. Moreover, the performance of the magnet arrangement is not constant along the longitudinal axis of the receiving space. It can be seen in FIGS. 2b and 2c that the peak strength of the fringe magnetic field acting in the receiving space between the top magnet (10) and the peak strength of the fringe magnetic field acting in the receiving space between the bottom magnet (10″) is weaker than the peak strength of the fringe magnetic field acting in the receiving space between the middle magnet (10′). The peak strength of the fringe magnetic field varies along the longitudinal axis of the receiving space due to the configuration of the repelling poles. Since the peak strength varies, the gradient of the fringe magnetic field also varies along the longitudinal axis of the receiving space. As a direct consequence, the performance of the magnet arrangement is not consistent along the longitudinal axis of the receiving space the efficiency and accuracy of the separating process is compromised.
Accordingly, there is a need to provide a magnetic separation device that can alleviate and/or overcome at least some of the above-mentioned problems. More specifically, the invention seeks to provide a magnetising portion that generates a high-gradient magnetic field suitable for isolating any size of magnetically labelled particles, including nanommeter sized particles. The invention seeks to reduce the separation time by providing a magnetising portion with a high-gradient magnetic field suitable for attracting and separating magnetically labelled particles quickly. The present invention also seeks to provide a magnetising portion that produces a high-gradient magnetic field with at least a substantially constant performance.